African American men have the highest rates of prostate cancer and the death rates due to prostate cancer are two times higher than Caucasians. The reason for the disparity is still unclear, but recent scientific studies suggest that the genetic and molecular changes in different ethnics are responsible for the disparity in African American men. These changes are responsible for different clinical outcome of prostate cancer in African American. Recent preliminary study showed that differences at molecular levels in prostate tissues between African American and Caucasian do exist. Therefore, we would like to further identify the molecules associated with prostate cancer racial disparity at the protein level using our novel Proteomic Pathway Array method, and to understand the mechanism of these molecules as a cause of the health disparity for prostate cancer among African American men. The success of the proposed study will have a profound benefit on the health of men, especially African Americans. The search for molecules that can distinguish those patients who will develop aggressive prostate cancer from those who will have a less aggressive course can help to identify patients who need more close surveillance and treatment. Furthermore, the identification and functional studies of molecules responsible for the aggressive behavior of prostate cancer in African American will help to design anti-cancer drugs and strategies. The translation from the discovery from this study to clinical application (diagnosis and treatment) can be achieved at a short period of time after completion of this study. The potential contributions ofthe study to advance health disparity research will be 1) identify biomarkers for prostate cancer racial disparity, 2) provide molecular bases why there is a racial difference in prostate cancer, 3) open a brand new way to look into the causes of racial difference in prostate cancer. PUBLIC HEALTH RELEVANCE: This study will lead to discovery of novel signal transduction proteins involved in racial disparity of prostate cancer and will generate clinically relevant information for developing biomarkers for early detection of aggressive prostate cancer in the African American community. The functional study of these signal transduction proteins in the context of racial disparity may lead to development of novel treatment strategy for prostate cancer according to ethnic background.